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Dhani NC , Hirte HW , Wang L , Burnier JV , Jain A , Butler MO , Welch S , Fleming GF , Hurteau J , Matsuo K , Matei D , Jimenez W , Johnston C , Cristea M , Tonkin K , Ghatage P , Lheureux S , Mehta A , Quintos J , Tan Q , Kamel-Reid S , Ludkovski O , Tsao MS , Wright JJ , Oza AM
Phase II Trial of Cabozantinib in Recurrent/Metastatic Endometrial Cancer: A Study of the Princess Margaret, Chicago, and California Consortia (NCI9322/PHL86)
Clin Cancer Res. 2020 Jun 1;26(11) :2477-2486
PMID: 31992589    PMCID: PMC7269808    URL: https://www.ncbi.nlm.nih.gov/pubmed/31992589
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PURPOSE: The relevance of the MET/hepatocyte growth factor pathway in endometrial cancer tumor biology supports the clinical evaluation of cabozantinib in this disease. PATIENTS AND METHODS: PHL86/NCI#9322 (NCT01935934) is a single arm study that evaluated cabozantinib (60 mg once daily) in women with endometrial cancer with progression after chemotherapy. Coprimary endpoints were response rate and 12-week progression-free-survival (PFS). Patients with uncommon histology endometrial cancer (eg, carcinosarcoma and clear cell) were enrolled in a parallel exploratory cohort. RESULTS: A total of 102 patients were accrued. Among 36 endometrioid histology patients, response rate was 14%, 12-week PFS rate was 67%, and median PFS was 4.8 months. In serous cohort of 34 patients, response rate was 12%, 12-week PFS was 56%, and median PFS was 4.0 months. In a separate cohort of 32 patients with uncommon histology endometrial cancer (including carcinosarcoma), response rate was 6% and 12-week PFS was 47%. Six patients were on treatment for >12 months, including two for >30 months. Common cabozantinib-related toxicities (>30% patients) included hypertension, fatigue, diarrhea, nausea, and hand-foot syndrome. Gastrointestinal fistula/perforation occurred in four of 70 (6%) patients with serous/endometrioid cancer and five of 32 (16%) patients in exploratory cohort. We observed increased frequency of responses with somatic CTNNB1 mutation [four partial responses (PRs) in 10 patients, median PFS 7.6 months] and concurrent KRAS and PTEN/PIK3CA mutations (three PRs in 12 patients, median PFS 5.9 months). CONCLUSIONS: Cabozantinib has activity in serous and endometrioid histology endometrial cancer. These results support further evaluation in genomically characterized patient cohorts.
Dhani, Neesha C Hirte, Hal W Wang, Lisa Burnier, Julia V Jain, Angela Butler, Marcus O Welch, Stephen Fleming, Gini F Hurteau, Jean Matsuo, Koji Matei, Daniela Jimenez, Waldo Johnston, Carolyn Cristea, Mihaela Tonkin, Katia Ghatage, Prafull Lheureux, Stephanie Mehta, Anjali Quintos, Judy Tan, Qian Kamel-Reid, Suzanne Ludkovski, Olga Tsao, Ming-Sound Wright, John J Oza, Amit M eng HHSN261201100032C/CA/NCI NIH HHS/ N01CM62203/CA/NCI NIH HHS/ Clin Cancer Res. 2020 Jun 1;26(11):2477-2486. doi: 10.1158/1078-0432.CCR-19-2576. Epub 2020 Jan 28.